Utility of Natural Product Biosynthetic Enzymes for Drug Discovery
Dr. Singh is interested in the structural diversification of natural products to develop drug candidates with biological activity against cancer and infectious diseases. Her research focuses on utility and rationally engineering enzymes to modify substrate acceptability profiles and develop novel drugs with improved activity. Natural products and their derivatives account for about three-quarters of the approved drugs on the market. Using conventional chemical synthesis to structurally diversify complex natural products can be challenging. To overcome this challenge, the Singh Laboratory engineers enzymes for proficiency, promiscuity, or altered substrate specificity, capable of performing regio- and stereo-specific transformations in order to generate a library of new drug-like molecules for screening. Recently, she has developed a platform for drug discovery through engineering the substrate specificity of prenyltransferases, a class of natural product late-stage modification enzymes. In this seminar, she will discuss the development of this prenyltransferase-based chemoenzymatic platform to diversify natural products with a library of novel substrates in order to generate therapeutically relevant molecules with enhanced activity against antimicrobial-resistant bacterial strains. Dr. Singh obtained her PhD from the Tata Institute of Fundamental Research, and subsequently pursued post-doctoral research at the Memorial Sloan Kettering Cancer Center in the United States, and Utrecht University in the Netherlands.